This project will develop a novel class of optical molecular imaging probes that exhibit a magnetomotive response to alter optical contrast when excited by a controllable external magnetic field. Investigational methods for in vivo molecular imaging of targeted magnetomotive probes are demonstrated using optical coherence tomography (OCT). This method will provide a unique resolution scale for the in vivo study and characterization of disease, for high detection sensitivity and dynamic range of induced optical contrast, for the evaluation of the efficacy of targeted drugs, and for basic biomedical research on the pharmacokinetic properties of these magnetomotive molecular probes. This proposal addresses the current need for highly sensitive and specific in vivo molecular imaging that has potential clinical utility. Magnetomotive-OCT (MMOCT), with micron-scale resolution combined with millimeters of penetration, will serve in investigating the dimensional- and surfactant-dependence of probe extravasation and diffusion. Externally-applied magnetomotive forces can be optimized in situ for highly sensitive detection, and can also be used to elucidate the binding strengths and ratios of the probes to their targeted sites. The potential of these probes for contrast in MRI and ultrasonic imaging, and their use in hyperthermic therapy and ultrasound-mediated drug delivery suggests a wide array of future translational investigations with unique capabilities for improving currently available cancer therapies. Specifically, we aim to: 1) Fundamentally understand the magnetomotive contrast of these molecular probes and produce probes optimized for the tissue type and desired information, 2) Develop novel, biocompatible, molecularly-targeted magnetomotive probes with high circulation time, low non-specific uptake, and magnetically-inducible optical contrast, 3) Determine efficacy of probes in targeting tumor cells using in vitro cell assays, and 4) Investigate the delivery mechanisms, extravasation, and specific uptake of targeted agents in vivo in a carcinogen-induced rat mammary tumor model using MMOCT with particular emphasis on tumor uptake at various stages of growth. These aims are synergistic, with the goal of producing optimized magnetomotive molecular probes for a given application (early-stage diagnosis or therapy). Conversely, we expect that the capability afforded by MMOCT to screen for efficacy and specificity will drive further development of more effective probes. [unreadable] [unreadable]